A 13-24 C-terminal peptide related to PF4 accelerates hematopoietic recovery of progenitor cells in vivo in mice treated with 5-fluorouracil.
We have recently reported that platelet factor 4 (PF4), a megakaryocyte-platelet protein, is a potent inhibitor of human and murine megakaryocytopoiesis. In addition, PF4 accelerated the recovery of the marrow precursor cells in 5-fluorouracil (5-FU) treated mice. We show in this study that a slight modification of the C-terminal peptide related to PF4 (C13-24DE), which was previously reported as the carboxy terminal region of PF4 implicated in PF4 inhibitory activity, is also able to significantly increase murine high proliferating-potential-colony forming cells (HPP-CFC), colony-forming-unit megakaryocyte (CFU-MK) and colony-forming unit granulocyte-macrophage (CFU-GM) progenitor number, eight days after 5-FU administration, when it was given intraperitoneally twice a day (200 micrograms/kg/inj) prior to 5-FU administration (150 mg/kg). Furthermore, the C13-24DE pretreatment enhanced both the number and the diameter of single megakaryocyte (MK) by day 8. These data indicate that the C13-24DE peptide related to PF4 accelerated the in vivo recovery of stem cells, progenitors (CFU-GM, CFU-MK) and single MK after 5-FU treatment and may have a hemoprotective effect against chemotherapeutic agents.
Aïdoudi
S
S
Institut des Vaisseaux et du Sang, Hôpital Lariboisière, Paris, France.
Lebeurier
I
I
Amiral
J
J
Quentin
G
G
Caen
J P
JP
Han
Z C
ZC
D000595:Amino Acid Sequence; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001798:Blood Proteins; D004353:Drug Evaluation, Preclinical; D005472:Fluorouracil / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D010978:Platelet Factor 4 / Q000494:pharmacology*
D000964:Antimetabolites, Antineoplastic; D001798:Blood Proteins; C110823:C13-24DE peptide; D010455:Peptides; D010978:Platelet Factor 4; D005472:Fluorouracil